The role of SNP-loop diuretic interactions in hypertension across ethnic groups in HyperGEN

Lisa De las Fuentes, Yun Ju Sung, Karen L. Schwander, Sonia Kalathiveetil, Steven Hunt, Donna K. Arnett, D. C. Rao

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Blood pressure (BP) is significantly influenced by genetic factors; however, less than 3% of the BP variance has been accounted for by variants identified from genome-wide association studies (GWAS) of primarily European-descent cohorts. Other genetic influences, including gene-environment (GxE) interactions, may explain more of the unexplained variance in BP. African Americans (AA) have a higher prevalence and earlier age of onset of hypertension (HTN) as compared with European Americans (EA); responses to anti-hypertensive drugs vary across race groups. To examine potential interactions between the use of loop diuretics and HTN traits, we analyzed systolic (SBP) and diastolic (DBP) blood BP from 1222 AA and 1231 EA participants in the Hypertension Genetic Epidemiology Network (HyperGEN). Population-specific score tests were used to test associations of SBP and DBP, using a panel of genotyped and imputed single nucleotide polymorphisms (SNPs) for AA (2.9 million SNPs) and EA (2.3 million SNPs). Several promising loci were identified through gene-loop diuretic interactions, although no SNP reached genome-wide significance after adjustment for genomic inflation. In AA, SNPs in or near the genes NUDT12, CHL1, GRIA1, CACNB2, and PYHIN1 were identified for SBP, and SNPs near ID3 were identified for DBP. For EA, promising SNPs for SBP were identified in ESR1 and for DBP in SPATS2L and EYA2. Among these SNPs, none were common across phenotypes or population groups. Biologic plausibility exists for many of the identified genes, suggesting that these are candidate genes for regulation of BP and/or anti-hypertensive drug response. The lack of genome-wide significance is understandable in this small study employing gene-drug interactions. These findings provide a set of prioritized SNPs/candidate genes for future studies in HTN. Studies in more diversified population samples may help identify previously missed variants.

Original languageEnglish
Article number00304
JournalFrontiers in Genetics
Volume4
Issue numberDEC
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Sodium Potassium Chloride Symporter Inhibitors
Molecular Epidemiology
Ethnic Groups
Single Nucleotide Polymorphism
Hypertension
African Americans
Blood Pressure
Genes
Antihypertensive Agents
Genome
Gene-Environment Interaction
Genome-Wide Association Study
Economic Inflation
Drug Interactions
Age of Onset
Population Groups
Population
Phenotype

Keywords

  • African americans
  • Blood pressure
  • European americans
  • Gene-drug interaction
  • Genome-wide association
  • Hypertension
  • Loop diuretic

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Cite this

De las Fuentes, L., Sung, Y. J., Schwander, K. L., Kalathiveetil, S., Hunt, S., Arnett, D. K., & Rao, D. C. (2013). The role of SNP-loop diuretic interactions in hypertension across ethnic groups in HyperGEN. Frontiers in Genetics, 4(DEC), [00304]. https://doi.org/10.3389/fgene.2013.00304

The role of SNP-loop diuretic interactions in hypertension across ethnic groups in HyperGEN. / De las Fuentes, Lisa; Sung, Yun Ju; Schwander, Karen L.; Kalathiveetil, Sonia; Hunt, Steven; Arnett, Donna K.; Rao, D. C.

In: Frontiers in Genetics, Vol. 4, No. DEC, 00304, 2013.

Research output: Contribution to journalArticle

De las Fuentes, L, Sung, YJ, Schwander, KL, Kalathiveetil, S, Hunt, S, Arnett, DK & Rao, DC 2013, 'The role of SNP-loop diuretic interactions in hypertension across ethnic groups in HyperGEN', Frontiers in Genetics, vol. 4, no. DEC, 00304. https://doi.org/10.3389/fgene.2013.00304
De las Fuentes, Lisa ; Sung, Yun Ju ; Schwander, Karen L. ; Kalathiveetil, Sonia ; Hunt, Steven ; Arnett, Donna K. ; Rao, D. C. / The role of SNP-loop diuretic interactions in hypertension across ethnic groups in HyperGEN. In: Frontiers in Genetics. 2013 ; Vol. 4, No. DEC.
@article{c420ce1bd40c41ef98a5e668531f2b95,
title = "The role of SNP-loop diuretic interactions in hypertension across ethnic groups in HyperGEN",
abstract = "Blood pressure (BP) is significantly influenced by genetic factors; however, less than 3{\%} of the BP variance has been accounted for by variants identified from genome-wide association studies (GWAS) of primarily European-descent cohorts. Other genetic influences, including gene-environment (GxE) interactions, may explain more of the unexplained variance in BP. African Americans (AA) have a higher prevalence and earlier age of onset of hypertension (HTN) as compared with European Americans (EA); responses to anti-hypertensive drugs vary across race groups. To examine potential interactions between the use of loop diuretics and HTN traits, we analyzed systolic (SBP) and diastolic (DBP) blood BP from 1222 AA and 1231 EA participants in the Hypertension Genetic Epidemiology Network (HyperGEN). Population-specific score tests were used to test associations of SBP and DBP, using a panel of genotyped and imputed single nucleotide polymorphisms (SNPs) for AA (2.9 million SNPs) and EA (2.3 million SNPs). Several promising loci were identified through gene-loop diuretic interactions, although no SNP reached genome-wide significance after adjustment for genomic inflation. In AA, SNPs in or near the genes NUDT12, CHL1, GRIA1, CACNB2, and PYHIN1 were identified for SBP, and SNPs near ID3 were identified for DBP. For EA, promising SNPs for SBP were identified in ESR1 and for DBP in SPATS2L and EYA2. Among these SNPs, none were common across phenotypes or population groups. Biologic plausibility exists for many of the identified genes, suggesting that these are candidate genes for regulation of BP and/or anti-hypertensive drug response. The lack of genome-wide significance is understandable in this small study employing gene-drug interactions. These findings provide a set of prioritized SNPs/candidate genes for future studies in HTN. Studies in more diversified population samples may help identify previously missed variants.",
keywords = "African americans, Blood pressure, European americans, Gene-drug interaction, Genome-wide association, Hypertension, Loop diuretic",
author = "{De las Fuentes}, Lisa and Sung, {Yun Ju} and Schwander, {Karen L.} and Sonia Kalathiveetil and Steven Hunt and Arnett, {Donna K.} and Rao, {D. C.}",
year = "2013",
doi = "10.3389/fgene.2013.00304",
language = "English",
volume = "4",
journal = "Frontiers in Genetics",
issn = "1664-8021",
publisher = "Frontiers Media S. A.",
number = "DEC",

}

TY - JOUR

T1 - The role of SNP-loop diuretic interactions in hypertension across ethnic groups in HyperGEN

AU - De las Fuentes, Lisa

AU - Sung, Yun Ju

AU - Schwander, Karen L.

AU - Kalathiveetil, Sonia

AU - Hunt, Steven

AU - Arnett, Donna K.

AU - Rao, D. C.

PY - 2013

Y1 - 2013

N2 - Blood pressure (BP) is significantly influenced by genetic factors; however, less than 3% of the BP variance has been accounted for by variants identified from genome-wide association studies (GWAS) of primarily European-descent cohorts. Other genetic influences, including gene-environment (GxE) interactions, may explain more of the unexplained variance in BP. African Americans (AA) have a higher prevalence and earlier age of onset of hypertension (HTN) as compared with European Americans (EA); responses to anti-hypertensive drugs vary across race groups. To examine potential interactions between the use of loop diuretics and HTN traits, we analyzed systolic (SBP) and diastolic (DBP) blood BP from 1222 AA and 1231 EA participants in the Hypertension Genetic Epidemiology Network (HyperGEN). Population-specific score tests were used to test associations of SBP and DBP, using a panel of genotyped and imputed single nucleotide polymorphisms (SNPs) for AA (2.9 million SNPs) and EA (2.3 million SNPs). Several promising loci were identified through gene-loop diuretic interactions, although no SNP reached genome-wide significance after adjustment for genomic inflation. In AA, SNPs in or near the genes NUDT12, CHL1, GRIA1, CACNB2, and PYHIN1 were identified for SBP, and SNPs near ID3 were identified for DBP. For EA, promising SNPs for SBP were identified in ESR1 and for DBP in SPATS2L and EYA2. Among these SNPs, none were common across phenotypes or population groups. Biologic plausibility exists for many of the identified genes, suggesting that these are candidate genes for regulation of BP and/or anti-hypertensive drug response. The lack of genome-wide significance is understandable in this small study employing gene-drug interactions. These findings provide a set of prioritized SNPs/candidate genes for future studies in HTN. Studies in more diversified population samples may help identify previously missed variants.

AB - Blood pressure (BP) is significantly influenced by genetic factors; however, less than 3% of the BP variance has been accounted for by variants identified from genome-wide association studies (GWAS) of primarily European-descent cohorts. Other genetic influences, including gene-environment (GxE) interactions, may explain more of the unexplained variance in BP. African Americans (AA) have a higher prevalence and earlier age of onset of hypertension (HTN) as compared with European Americans (EA); responses to anti-hypertensive drugs vary across race groups. To examine potential interactions between the use of loop diuretics and HTN traits, we analyzed systolic (SBP) and diastolic (DBP) blood BP from 1222 AA and 1231 EA participants in the Hypertension Genetic Epidemiology Network (HyperGEN). Population-specific score tests were used to test associations of SBP and DBP, using a panel of genotyped and imputed single nucleotide polymorphisms (SNPs) for AA (2.9 million SNPs) and EA (2.3 million SNPs). Several promising loci were identified through gene-loop diuretic interactions, although no SNP reached genome-wide significance after adjustment for genomic inflation. In AA, SNPs in or near the genes NUDT12, CHL1, GRIA1, CACNB2, and PYHIN1 were identified for SBP, and SNPs near ID3 were identified for DBP. For EA, promising SNPs for SBP were identified in ESR1 and for DBP in SPATS2L and EYA2. Among these SNPs, none were common across phenotypes or population groups. Biologic plausibility exists for many of the identified genes, suggesting that these are candidate genes for regulation of BP and/or anti-hypertensive drug response. The lack of genome-wide significance is understandable in this small study employing gene-drug interactions. These findings provide a set of prioritized SNPs/candidate genes for future studies in HTN. Studies in more diversified population samples may help identify previously missed variants.

KW - African americans

KW - Blood pressure

KW - European americans

KW - Gene-drug interaction

KW - Genome-wide association

KW - Hypertension

KW - Loop diuretic

UR - http://www.scopus.com/inward/record.url?scp=84892427620&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892427620&partnerID=8YFLogxK

U2 - 10.3389/fgene.2013.00304

DO - 10.3389/fgene.2013.00304

M3 - Article

VL - 4

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

IS - DEC

M1 - 00304

ER -